The objective of this R03 proposal is to identify physiological correlates associated with anxiety in youth with atopic dermatitis (AD), a chronic and often psychosocially devastating skin disorder commonly known as eczema. The investigation posits an association between anxiety and allergic inflammation, the pathophysiological hallmark of AD. This model is derived from a confluence of studies indicating that: 1) anxiety is associated with AD, 2) anxiety and stress exacerbate AD inflammatory lesions, 3) AD dermatological severity improves with primary anxiety-based treatments, and 4) AD is associated with localized and systemic inflammatory changes. The association between anxiety and AD suggests that these disorders may share pathophysiological mechanisms of disease. If so, AD may be a unique medical model in which to investigate specific biological mediators associated with anxiety in youth. Existing AD studies do not extend beyond examining the association between AD dermatological severity and anxiety, and results of these studies are inconclusive. No studies have examined the association between anxiety and specific allergic inflammatory mediators central to the pathophysiology of AD. Moreover, there is a wealth of empirical data supporting a relationship between anxiety and respiration, and more specifically, between anxiety and asthma, an atopic disorder that commonly co-exists with AD. No studies have investigated whether the association between anxiety and AD in youth is related to co-morbid pulmonary inflammation, the pathophysiological hallmark of asthma. This study tests the novel hypothesis that anxiety is associated with specific biological measures of allergic inflammation in youth with AD. Subjects will include a well-defined clinical sample of 30 youth (age 13 to 18 years) with AD and a community matched healthy control group of 30 youth. The Specific Aims of this study examine the prevalence of anxiety disorders and the severity of anxiety symptoms in youth with AD compared to healthy controls using standardized and validated psychometric measures; and assess the relationship between anxiety symptoms and three physiologically distinct markers of AD allergic inflammation known to correlate with AD disease severity: 1) Dermatological inflammation, determined by the SCORAD Index, a standardized clinical evaluation of AD severity; 2) Systemic inflammation, assessed by peripheral blood levels of eosinophil proteins (eosinophil cationic protein and major basic protein); and 3) Pulmonary inflammation, innovatively assessed with the noninvasive measurement of exhaled nitric oxide and carbon monoxide levels. The study is significant in testing a novel neurobiological model of anxiety that may open new doors to the medical assessment and treatment of anxiety disorders in children and adolescents at large. Pilot data generated from this study will serve as a foundation for the principal investigator's R01 application to pursue additional neurobiological studies of anxiety in youth. [unreadable] [unreadable]